The nuclear receptors constitute a class of conserved transcription factors that function in regulating animal development. Two NR2E subclass nuclear receptors found in C. elegans,
fax-1 and
nhr-67, function in different hermaphrodite gonad cells to coordinate aspects of cell differentiation, in addition to roles already described in neuron differentiation.The C. elegans
fax-1 gene is the ortholog of PNR in vertebrates. We have found that
fax-1 is expressed in the migrating DTCs of the hermaphrodite gonad from late L2 through L4. Loss of
fax-1 results in a low-penetrance DTC migration defect and a high penetrance brood size defect. The reduction in offspring appears to result from a defect in spermatogenesis rather than oogenesis. In
vab-3 mutants, the DTCs continue to migrate into adulthood and also fail to turn off
fax-1, suggesting that expression of
fax-1 is a property of a migrating DTC. We propose that
fax-1 function in DTC migration is a robustness phenomenon, in contrast to the more demanding requirement for hermaphrodite spermatogenesis.The C. elegans tailless ortholog,
nhr-67, is expressed in a dynamic pattern in pre-uterine cells: initially in the 4 pre-VU cells during the L2, then upregulated in the anchor cell (AC) in response to the
lin-12/lag-2 Notch reciprocal signaling system. During the L3 stage,
nhr-67 expression is maintained at high levels in the AC and at low levels in VU descendants that produce the adult ventral uterus.
nhr-67 is required for expression of the
lin-12/Notch receptor in pre-VU and VU cells and for multiple markers of AC identity, indicating that it functions in differentiation of both uterine cell types.Deletion of a 276bp region of the
nhr-67 promoter results in a loss of
nhr-67 expression in pre-VU, AC, and VU cells. Expression of 276bp region::gfp shows the region is necessary and sufficient for
nhr-67 pre-VU and AC expression. The region includes two E box sequences that we propose bind the HLH-2 transcription factor, which functions in AC and pre-VU development. We have performed site-directed mutagenesis to delete the E boxes and other conserved elements from the 276bp promoter region and tested their functions directly in vivo. One site can be bound by the SEX-1 nuclear receptor, which has a modest role in regulating
nhr-67 expression. Our data demonstrate the primary role of the E box sequences in regulating
nhr-67 in the gonad.Funded by NIGMS..